BCH425H (JBB1425)

Structural Biology: Principles and Practice

BCH425H (JBB1425)

The structure, dynamics, and energetics of biological systems can be investigated using biophysical techniques that involve the absorption, emission, and scattering of electromagnetic radiation and particles. This course provides a detailed overview of structural biology approaches used for the study of macromolecules (particularly proteins and nucleic acids) so that students will be able to understand journal articles and seminars dealing with these methods, as well as how these techniques can be applied to answer important questions in biochemistry or molecular biology. While many different methods will be surveyed, the emphasis is on those techniques that enable atomic or near-atomic level descriptions of macromolecular structure: X-ray crystallography, NMR spectroscopy, and electron cryomicroscopy.

Since critical interpretation of the measured parameters requires an understanding of the underlying principles, lectures will focus on providing knowledge of the underlying physical basis of the methods. Potential applications will also be discussed, with a focus on the kinds of information that can be learned from each techniques. Practical aspects surrounding experimental issues and limitations will also be covered, as will the integration of multiple methodologies to solve key questions in structural biology.

Topics covered will include the theory and practice of optical spectroscopy in the study of conformations of proteins and nucleic acids; electron cryomicroscopy applied to macromolecular structure from 2D crystals and and unordered single particles; the physical principles and analytic uses of NMR spectroscopy in the study of protein structure and dynamics; X-ray diffraction on single crystals and its use as a tool in elucidating the three- dimensional fold of proteins, ligand binding sites and enzymatic mechanisms.